细胞周期调控基因多态与氯乙烯接触工人染色体损伤的易感性

Genetic polymorphism in cell cycle control genes and susceptibility of chromosomal damage in vinyl chloride monomer exposed workers

目的探讨细胞周期调控基因P53、P21和细胞周期蛋白D1基因多态与氯乙烯致外周血淋巴细胞染色体损伤易感性的关系。方法采用胞质分裂阻滞微核试验方法评价183名氯乙烯接触工人染色体损伤水平,应用聚合酶链反应-限制性片段多态性技术对P53第4外显子、第3和6内含子,P21第2外显子和第3外显子的3′非翻译区,以及CCND1基因第4外显子等多态位点进行检测。结果研究对象P53基因第4外显子,第3和6内含子等位基因的突变频率分别为0.45,0.04,0.05,P21第2外显子和第3外显子两个位点的突变频率分别为0.37和0.50,CCND1第4外显子突变频率为0.42。多因素Poisson回归分析结果表明,30岁以上年龄组的人群发生染色体损伤的危险度是30岁以下年龄组人群的1.2202倍,差异有统计学意义(OR=1.2202,95%CI:1.0580～1.4072,P=0.0062);女性发生染色体损伤的危险度是男性的1.1491倍,差异有统计学意义(OR=I.1491,95%CI:0.9841～1.3416,P=0.0772);P53第6内含子突变基因型人群发生染色体损伤的危险度是野生基因型人群的1.3032倍,差异有统计学意义(OR=1.3032,95%CI:1.1285～1.6405,P=0.0285)。P53单倍型分析结果表明,携带BBB/AAA和BAB/AAA单倍型对(按照P53第4外显子、第3和6内含子顺序,B表示突变型,A表示野生型)的人群微核率与野生型AAA/AAA人群相比,OR值分别为1.4418(95%CI:1.0316～2.0152)和1.7100(95%CI:1.0385～2.8157)。结论氯乙烯暴露人群中,30岁以上、女性、P53 INTRON6等位基因突变以及P53第4外显子,第3和第6内含子单倍型对为BBB/AAA和BAB/AAA都是个体发生染色体损伤的危险因素。

Objective To explore the relationship between genetic polymorphism of P53, P21, CCND1 and susceptibility of chromosomal damage induced by vinyl chloride monomer （VCM）. Methods 183 workers occupationally exposed to VCM were involved in our study. Cytokinesis-block micronucleus （CB-MN） assay was used to detect chromosome damage in peripheral lymphocyte. PCR-RFLP technique was applied to detect polymorphisms in P53 gene （exon4, intron3 and intron6）, P21 gene （exon2 and exon3） and CCND1 （exon4）. Results The risk of chromosomal damage for VCM-exposed workers with more than 30 yr was 1.2202（95% CI： 1.0580-1.4072, P=-0.0062） compared with the younger workers, and the risk of female workers was 1.1491 （95% CI： 0.9841-1.3416, P--0.0772） compared with male workers. The MN frequency in subjects with P53 intron6 mutant homozygous and heterozygous was higher than their wild-type homozygous counterparts （OR=1.3032, 95% CI： 1.1285-1.6405, P--0.0285）. P53 exon4, intron3 and intron6 haplotype pairs of BBB/AAA and BAB/AAA were associated with the increased frequencies of micronucleus. Conclusion Among VCM-exposed workers, more than 30ys, female, carrying P53 intron6 mutated allele and BBB/AAA 和 BAB/AAA haplotype pairs have higher risk of chromosomal damage.